Study of the reactions between platinum(II) complexes and L-methionine in the presence and absence of 5'-GMP

The reactions of the platinum(II) complexes, [Pt(dien)(H(2)O)](2+), [PtCl(dien)](+) and [PtBr(dien)](+) (dien is diethylenetriamine) with some biologically relevant ligands such as inosine (INO), inosine-5'-monophosphate (5'-IMP), guanosine-5'-monophosphate (5'-GMP), glutathione (GSH) and l-methionine (S-meth), have been studied by UV-Visible spectrophotometry and (1)H NMR spectroscopy. Kinetic and thermodynamic parameters of these reactions were determined. Competitive reactions of [PtCl(dien)](+) with l-methionine and 5'-GMP demonstrated initially rapid formation of [Pt(dien)(S-meth)](2+) followed by displacement of l-methionine by 5'-GMP. In the later stages the concentration of [Pt(dien)(N7-GMP)](2+) is predominant. The results are analyzed in reference to the anti-tumour activity of Pt(II) complexes.     

Effects of amine ligand bulk and hydrogen bonding on the rate of reaction of platinum(II) diamine complexes with key nucleotide and amino acid residues

NMR spectroscopy has been used to observe the effects of the amine ligand on the rate of reaction of platinum diamine and triamine complexes with DNA and protein residues. Whereas [Pt(dien)Cl]Cl and [Pt(dien)(D(2)O)](2+) have been known to react faster with thioether residues such as N-AcMet than with 5'-GMP, we found that [Pt(Me(4)en)(D(2)O)(2)](2+) appeared to react faster with 5'-GMP. To quantitatively assess the factors influencing the rates of reaction, rate constants at pH 4 were determined for the reactions of [Pt(en)(D(2)O)(2)](2+) [en = ethylenediamine] and [Pt(Me(4)en)(D(2)O)(2)](2+) with N-AcMet, N-AcHis, 5'-GMP, and Guo (guanosine). In each case the less bulky complex ([Pt(en)(D(2)O)(2)](2+)) reacts more quickly than does the bulkier [Pt(Me(4)en)(D(2)O)(2)](2+), as expected. Both complexes reacted faster with 5'-GMP; however, analysis of the rate constants suggests that the [Pt(en)(D(2)O)(2)](2+) complex favors reaction with 5'-GMP due to hydrogen bonding with the 5'-phosphate, whereas [Pt(Me(4)en)(D(2)O)(2)](2+) disfavors reaction with N-AcMet due to steric clashes. Bulk had relatively little effect on the rate constant with N-AcHis, suggesting that peptides or proteins that coordinate via His residues would not have their reactivity affected by bulky diamine ligands.     

(Dien)M(II) (M=Pd, Pt) and (NH3)3Pt(II) complexes of 1-methylcytosine: Linkage and rotational isomerism, metal-promoted deamination, and pathways to dinuclear species

Despite their structural similarity, [Pt(dien)(1-MeC-N3)](2+) (1), [Pd(dien)(1-MeC-N3)](2+) (2), and [Pt(NH(3))(3)(1-MeC-N3)](2+) (3) (with dien=diethylenetriamine and 1-MeC=neutral 1-methylcytosine) behave in part markedly different at strongly alkaline pH (12-13) and at room temperature. While 1 and 2, yet not 3 show linkage isomerization from N3 to N4, deamination of the cytosine nucleobase to 1-methyluracilate occurs with 1 and 3, yet not with 2. Pathways leading to N3,N4-diplatinated 1-MeC(-) complexes (1-MeC(-)=1-methylcytosine, deprotonated at exocyclic amino group N4) have been studied at high pH by starting from 1 and 3, respectively, and adding (dien)Pt(II). It appears that initial migration of the metal entity from N3 to N4, followed by binding of the second metal to the available N3 site, is favored over sequential coordination to N3 and then N4. X-ray crystal data of 1-3 density functional theory (DFT) calculations, and NMR ((1)H, (195)Pt) data are presented.     

Antiproliferative activity of mixed-ligand dien-Cu(II) complexes with thiazole, thiazoline and imidazole derivatives.

The reaction of [Cu(dien)NO(3)]NO(3) with 2-amino-5-methylthiazole (2A5MT), 2-amino-2-thiazoline (2A-2Tzn), imidazole (im), N,N'-thiocarbonyldiimidazole (Tcdim), 2-aminothiazole (2AT) and 2-ethylimidazole (2Etim), gave a new series of mixed-ligand compounds of the general formula [Cu(dien)(B)NO(3))]NO(3); (dien, diethylenetriamine; B, 2A5MT, 2A-2Tzn, im, Tcdim, 2AT and 2Etim). The complexes have been characterised by elemental analysis, molar conductivity and magnetic measurements, as well as by electronic and IR spectral studies. According to the above measurements the possible structure of the compounds is the square pyramidal in the solid state and the square planar in aqueous solution. We tested all complexes for antiproliferative (cytostatic and cytotoxic) activity against a panel of cell lines (HeLa, L929, HT-29 and T47D). All [(dien)Cu(B)NO(3))](NO(3)) complexes had an activity against colon cancer cells (HT-29), inducing G2/M cell cycle arrest, an effect that for most of the complexes could be attributed to p34cdc2 inhibition by tyrosine-phosphorylation and/or to induction of (cyclin-dependent kinase inhibitor) p21(WAF1). Other cell lines were resistant to the majority of the complexes, except [Cu(dien)(2A5MT)NO(3))](NO(3)), that had showed the highest anti-proliferative activity against HT-29 cells also. The predilection for colon cancer cells and the relatively low toxicity against normal (L929) cells justify further investigation of this group of compounds.     

In vivo anticancer, anti-inflammatory, and toxicity studies of mixed-ligand Cu(II) complexes of dien and its Schiff dibases with heterocyclic aldehydes and 2-amino-2-thiazoline. Crystal structure of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O)

A new series of complexes of the type [Cu(dien)(2a-2tzn)Y(2)] and [Cu(dienXX)(2a-2tzn)Y(2)], where dien=diethylenetriamine and dienXX=Schiff dibase of diethylenetriamine formed with 2-furaldehyde (dienOO), 2-thiophenecarboxaldehyde (dienSS), or pyrrol-2-carboxaldehyde (dienNN); Y=Cl, Br or NO(3); and 2a-2tzn=2-amino-2-thiazoline, were synthesized and their structure established by C, H, N and Cu analysis; IR and electronic spectra; magnetic susceptibility; and molar conductivity. The isolated complexes are monomers, paramagnetic, and electrolytes of types 1:1 or 1:2. In both types of solid state complexes, [Cu(dien)(2a-2tzn)Y(2)] and [Cu(dienXX)(2a-2tzn)Y(2)], dien and its Schiff dibases are bonded to Cu(II) in a tridentate fashion through 3N atoms. The coordination sphere is completed by the endocyclic nitrogen of the thiazoline moiety and by two Cl, Br, or NO(3) groups with distorted octahedral geometry. The proposed structure of these compounds was supported by X-ray analysis of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O). The coordination polyhedron around the copper atom can be described as a distorted square pyramid [Cu(dien)(Br)(2a-2tzn)](+). Its basal plane is occupied by the four nitrogen atoms of the dien and thiazoline ligands with Cu-N distances ranging between 1.996(6) and 2.032(3)A, and the axial position is occupied by one of the two bromine atoms (Br1) with a Cu1-Br1 bond distance of 2.782(1)A. The second bromine atom (Br2) is 4.694(2)A from the copper atom, which exists as a discrete anion and is responsible for the cationic nature of the complex. Results regarding toxicity, antitumor, and anti-inflammatory activities of the investigated compounds are promising and allow the selection of a lead compound for further biological studies.     

Model investigations for vanadium-protein interactions: vanadium(III) compounds with dipeptides and their oxovanadium(IV) analogues

The reaction of VCl(3) with 1,10-phenanthroline and a series of dipeptides (H(2)dip), having aliphatic as well as aromatic side chains, in methyl alcohol and in the presence of triethylamine affords vanadium(III) compounds of the general formula [V(III)(dip)(MeOH)(phen)]Cl. Aerial oxidation/hydrolysis of the vanadium(III) species gives their oxovanadium(IV) analogues of the general formula [V(IV)O(dip)(phen)]. X-ray crystallographic characterization of the [V(IV)O(dip)(phen)] compounds (where dip(2-)=Gly- L-Ala, Gly- L-Val and Gly- L-Phe) revealed that the vanadium atom possesses a severely distorted octahedral coordination and is ligated to a tridentate dip(2-) ligand at the N(amine) atom, the deprotonated N(peptide) atom and one of the O(carboxylate) atoms, as well as an oxo group and two phenanthroline nitrogen atoms. Circular dichroism characterization of the V(III)/V(IV)O(2+)-dipeptide compounds revealed a strong signal for the V(IV)O(2+) species in the visible range of the spectrum, with a characteristic pattern which may be exploited to identify the N(am), N(pep) and O(car) ligation of a peptide or a protein to V(IV)O(2+) center, and a weak Cotton effect of opposite sign to their vanadium(III) analogues. The visible spectra of the V(III)-dipeptide compounds revealed two d-d bands with high intensity, thus indicating that the covalency of the metal-donor atoms is significant, i.e. the vanadium d orbitals are significantly mixed with the ligand orbitals, and this is confirmed by the low values of their Racah B parameters. The high-intensity band of the V(IV)O(2+)-dipeptide compounds at approximately 460 nm implies also a strong covalency of the metal with the equatorial donor atoms and this was supported by the EPR spectra of these compounds. Moreover, the V(III)/V(IV)O(2+)-dipeptide complexes were characterized by EPR and IR spectroscopies as well as conductivity and magnetic susceptibility measurements.     

Interaction of (dien)Pd(II) with cytidine and cytidine 5'-monophosphate. Influence of the phosphate group on the kinetics and mechanism

The kinetics and the equilibrium of (dien)PdCl+ interaction with cytidine (C) and cytidine 5'-monophosphate (CMP) were studied by spectrophotometry and by stopped-flow methods. In both cases, the mechanism implies a (dien)Pd(H2O)2+ intermediate with a significant contribution of the solvent path at low chloride concentrations. With CMP, the rate is affected due to the addition of a mechanistic path via an intermediate formed between (dien)Pd(II) and the phosphate group of CMP. The kinetic and thermodynamic parameters have been determined and reflect the favorable electrostatic interactions due to the presence of the phosphate group of CMP. Furthermore, these parameters are in agreement with a transient (dien)Pd(II)-phosphate complex of CMP leading to the formation of the thermodynamically favored (dien)Pd(II)-N3 complex as final product.     

Bacterial sensors based on Acidithiobacillus ferrooxidans Part II. Cr(VI) determination

The aerobic acidophilic bacterium Acidithiobacillus ferrooxidans oxidizes Fe(2+) and S(2)O(3)(2-) ions by consuming oxygen. An amperometric biosensor was designed including an oxygen probe as transducer and a recognition element immobilized by a suitable home-made membrane. This biosensor was used for the indirect amperometric determination of Cr(2)O(7)(2-) ions owing to methods based on a mediator (Fe(2+)) or titration. Using the mediator, the biosensor response versus Cr(2)O(7)(2-) was linear up to 0.4 mmol L(-1), with a response time of, respectively, 51 s (2 x 10(-5) mol L(-1) Cr(2)O(7)(2-)) and 61 s (6 x 10(-5) mol L(-1) Cr(2)O(7)(2-)). The method sensitivity was 816 microA L mol(-1). Response time and measurement sensitivity depended on membrane material and technique for biomass immobilization. For example, their values were 90 s-200 microA L mol(-1) when using a glass-felt membrane and 540 s-4.95 microA L mol(-1) with a carbon felt one to determine a concentration of 2 x 10(-5) mol L(-1) Cr(2)O(7)(2-). For the titration method, the biosensor is used to determine the equivalence point. The relative error of quantitative analysis was lower than 5%.     

The kinetics and stereochemistry of base hydrolysis of the seven isomers of [Co(dien)(ampy)Cl] and [Co(dien)(ibn)Cl]

The kinetics and stereochemistry for the base catalysed substitution reactions of all seven isomers (4 mer and 3 fac) of both [Co(dien)(ibn)Cl]²⁺ and [Co(dien)(ampy)Cl]²⁺ have been studied in detail, for water and azide ion as entering groups. The stereochemistry for the azide ion anation of some of the [Co(dien)(diamine)OH]²⁺ species have also been investigated. The mer isomers are of comparable reactivity and amongst the fastest reacting pentaaminechlorocobalt(III) complexes known. They are also much faster to hydrolyse than the fac species. In both the ibn and ampy systems, a common product stereochemistry is observed for the four reactant mer isomers (the product is a mixture of all four mer configurations), for both azide ion and water as nucleophiles, but not for the three fac reactants (H₂O as nucleophile). The kinetic and equilibrium distributions are quite different. For the mer isomer reactions, a common trigonal bipyramidal five-coordinate intermediate deprotonated at the sec-NH of the dien is overwhelmingly implicated. The substitution mechanisms are argued in detail. Other data reported include isomerisation rates and equilibrium distributions for some mer-hydroxo and a mer-aqua complex of exceptional reactivity, equilibrium distributions for the mer-phosphato complexes in the ampy system under different pH conditions, the crystal structure for the isolated m1-[Co(dien)(ampy)OP(OH)₃]Cl₃ · 2H₂O species, and a rationale for its predominance at neutral pH based on internal H-bonding.     

Cytotoxicity studies of chromium(III) complexes on human dermal fibroblasts

The cytotoxicity of certain Cr(III) complexes, such as [Cr(salen)(H(2)O)(2)](+), [Cr(edta)(H(2)O)](-), [Cr(en)(3)](3+), [Cr(ox)(3)](3-), [Cr(pic)(3)], and CrCl(3), which differ in ionic character and ligand environment in human dermal skin fibroblasts, has been studied. After 72 h of exposure to 100 microM doses of chromium(III) complexes, the order in which the complexes had an inhibitory effect on cell viability was [Cr(en)(3)](3+) > [Cr(salen)(H(2)O)(2)](+) > [Cr(ox)(3)](3-) > [Cr(edta)(H(2)O)](-) > [Cr(pic)(3)] > CrCl(3). Based on viability studies it was confirmed that [Cr(en)(3)](3+), a triply charged cation, inhibits cell proliferation, and therefore, it was chosen to carry out further investigations. [Cr(en)(3)](3+), at a dose of 50 microM, was found to bring about surface morphological changes, evidenced by cellular blebbing and spike formation accompanied by nuclear damage. TEM analysis revealed substantial intracellular damage to fibroblasts in terms of the formation of apoptotic bodies and chromatin condensation, thus reflecting cell death. FACS analysis further revealed DNA damage by formation of a sub-G(1) peak with 84.2% DNA as aneuploid DNA and arrest of the G(2) / M phase of the cell cycle. Cellular DNA damage was confirmed by agarose gel electrophoresis with the characteristic appearance of a DNA streak in DNA isolated from [Cr(en)(3)](3+)-treated fibroblasts. The proposed mechanism suggests the plausible role of Cr(V), formed as a result of oxidation of Cr(III) by cellular oxidative enzymes, in the cytotoxic response. Consequently, any Cr(III) complex that is absorbed by cells and can be oxidized to Cr(V) must be considered a potential carcinogen. This has potential implications for the increased use of Cr(III) complexes as dietary supplements and highlights the need to consider the cytotoxicity and genotoxicity of a variety of Cr(III) complexes and to understand the potential hazards of Cr(III) complexes encountered in research laboratories.     

DNA-platinum interactions in vitro with trans- and cis-Pt(NH3)2Cl2.

In the present study the nature and the hydrolysis of DNA-Pt complexes with the platinum compounds, [Pt(dien)Cl]Cl, trans- and cis-Pt(NH3)2Cl2, using potentiometric chloride determinations, have been investigated. The trans-Pt(NH3)2Cl2 and the [Pt(dien)Cl]Cl react with the GC planes at the N7(G) sites, while the cis-Pt(NH3)2Cl2 compound reacts with the GC planes and forms a chelate by using the N7(G) and O6(G) sites. The complex is a specific 1:1 Pt:DNA adduct. The platinum atom in cis-Pt(NH3)2Cl2 liberates both chlorine atoms on chelation. A mechanism for the in vivo antitumor activity of the cis-Pt(NH3)2Cl2 is proposed and the structure activity relationship is discussed.     

Peroxidase-mediated in vitro metabolism of diethylstilbestrol and structural analogs with different biological activities

The comparative peroxidative metabolism of diethylstilbestrol (DES) and structurally related compounds of different biological activity was investigated in vitro with horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) as a model peroxidase system: UV spectroscopy revealed the formation of p-quinone intermediates in HRP-H2O2 catalyzed incubations of DES, 3',3",5',5"-tetrafluoro-DES (TF-DES) and dimethylstilbestrol (DMS) and the tautomerization of the quinones to their dien compounds, Z,Z-dienestrol (Z,Z-DIES), tetrafluoro-dienestrol (TF-DIES) and dienmestrol (DIMS) respectively, which were characterized by HPLC and GC/MS. Z,Z-DIES, E,E-DIES, TF-DIES and DIMS were subject to further peroxidative metabolism; however, quinone intermediates were not formed in the HRP-H2O2 containing incubations according to UV spectroscopy. Similarly, hexestrol (HES), 4'-O-methyl-DES (M-DES) and 4',4"-O-dimethyl-DES (DM-DES) did not form quinone intermediates; moreover, they showed little or no apparent metabolic conversion under conditions where DES, TF-DES and DMS were readily peroxidized. However, at a 20-fold higher peroxidase concentration HES and M-DES showed metabolic conversion whereas DM-DES did not.     

The preparation and characterization of Cr(III) and Co(III) complexes of GDP and GTP and their interactions with avian phosphoenolpyruvate carboxykinase

The exchange inert coordination complexes, Cr(H2O)4GDP, Cr(H2O)4GTP, Cr(NH3)4GDP, Cr(NH3)4GTP, Co(NH3)4GDP, and Co(NH3)4GTP have been synthesized and characterized. The lambda and delta coordination isomers of Cr(H2O)4GDP, Cr(NH3)4GDP, and the four Cr(H2O)4GTP isomers have been separated by reverse phase HPLC and characterized by their CD spectra. While the isomers of Co(NH3)4GTP have not been successfully separated, 31P NMR spectroscopy reveals the presence of the lambda and delta forms. The complexes, Cr(H2O)4GDP, Co(NH3)4GDP, Cr(H2O)4GTP, and Co(NH3)4GTP, are linear competitive inhibitors of avian phosphoenolpyruvate carboxykinase. The Ki values of 30 microM, 540 microM, 40 microM, and 12 microM, respectively, were determined for these complexes using Mn-IDP as the nucleotide substrate in the phosphoenolpyruvate carboxylation direction or Mn-ITP as nucleotide substrate for the oxalacetate decarboxylation reaction. The lambda and delta isomers of Cr(H2O)4 GDP show little specificity (a twofold maximum difference in Ki) for the enzyme. The isomeric forms of Cr(H2O)4 GTP demonstrate no observed stereoselectivity of interaction with the enzyme. All of the complexes tested, except for Cr(NH3)4GDP and Co(NH3)4GDP, which have larger Ki values, are good substrate analogs for P-enolpyruvate carboxykinase. When the substrate is Mn-GTP, fixed at 0.2 mM at pH 6.0, enzyme activity is stimulated two- to two and a half-fold by Cr(H2O)4GTP. A Dixon plot reveals that the stimulatory effect is saturated at 0.4 mM Cr(H2O)4GTP. The interaction of the enzyme with Cr(H2O)4GTP appears to produce a "memory" effect which is manifest with guanosine nucleotide substrates, but which is not observed with the alternative substrate Mn-ITP.     

Reactions of *NO2 with chromium(III) complexes with histamine and pyridoxamine ligands studied by the stopped-flow technique

This study demonstrated the direct formation of the nitrogen dioxide (*NO2) radical during the decomposition of 3-morpholinosydnonimine (SIN-1) in biological buffer 4-morpholinoethanosulfone acid solution. Consequently, at approximately pH 4, SIN-1 can be used successfully as a source of *NO2. This conclusion is drawn from a comparison of the reactions of cis-[Cr(C2O4)(L- L)(OH2)2]+, where L-L denotes pyridoxamine (Hpm) or histamine (hm), with the gaseous *NO2 radical obtained by two methods: from SIN-1 and from a simple redox reaction. These reactions were investigated using the stopped-flow technique. The measurements were carried out at temperatures ranging from 5 to 25 degrees C over a pH range from 6.52 to 9.11 for cis-[Cr(C2O4)(Hpm) (OH2)2]+ and from 6.03 to 8.15 for cis-[Cr(C2O4)(hm)(OH2)2] +. We also determined the thermodynamic activation parameter (E(a)) and the uptake mechanism for each of the coordination compounds studied.     

Aluminium(III), chromium(III) and iron(III) complexes with 5-iodouracil and 5-iodouracil-histidine and their antitumour activity

Complexes of the type [Al(HL)(OH)Cl(2)], [M(HL)(OH)(2)Cl] and [M'(HL)(L')(OH)Cl], where HL = 5-iodouracil; HL' = histidine; M = Cr(III), Fe(III) and M' = Al(III), Cr(III), Fe(III), were synthesized and characterized. The complexes are polymeric showing high decomposition points and are insoluble in water and common organic solvents. The mu(eff) values, electronic spectral bands and ESR spectra suggest a polymeric 6-coordinate spin-free octahedral stereochemistry for the Cr(III) and Fe(III) complexes. 5-Iodouracil acts as a monodentate ligand coordinating to the metal ion through the O atom of C((4)) = O while histidine through the O atom of -COO(- ) and the N atom of -NH(2) group. In vivo antitumour effect of 5-iodouracil and its complexes was examined on C(3)H /He mice against P815 murine mastocytoma. As evident from their T/C values, Cr(III) and Fe(III) complexes display significant and higher antitumour activity compared to the 5-iodouracil ligand. The in vitro results of the complexes on the same cells indicate that Cr(III) and Fe(III) complexes show higher inhibition on (3)H-thymidine and (3)H-uridine incorporation in DNA and RNA replication, respectively, at a dose of 5 microg/mL.     

Under proper control, oxidation of proteins with known chemical structure provides an accurate and absolute method for the determination of their molar concentration

Oxidation at 120 degrees C of inorganic and organic (including amino acids, di- and tripeptides) model compounds by K(2)Cr(2)O(7) in the presence of H(2)SO(4) (mass fraction: 0.572), Ag(2)SO(4) (catalyst), and HgSO(4) results in the quantitative conversion of their C-atoms into CO(2) within 24 h or less. Under these stressed, well-defined conditions, the S-atoms present in cysteine and cystine residues are oxidized into SO(3) while, interestingly, the oxidation states of all the other (including the N-) atoms normally present in a protein do remain quite unchanged. When the chemical structure of a given protein is available, the total number of electrons the protein is able to transfer to K(2)Cr(2)O(7) and thereof, the total number of moles of Cr(3+) ions which the protein is able to generate upon oxidation can be accurately calculated. In such cases, unknown protein molar concentrations can thus be determined through straightforward spectrophotometric measurements of Cr(3+) concentrations. The values of molar absorption coefficients for several well-characterized proteins have been redetermined on this basis and observed to be in excellent agreement with the most precise values reported in the literature, which fully assesses the validity of the method. When applied to highly purified proteins of known chemical structure (more generally of known atomic composition), this method is absolute and accurate (+/-1%). Furthermore, it is well adapted to series measurements since available commercial kits for chemical oxygen demand (COD) measurements can readily be adapted to work under the experimental conditions recommended here for the protein assay.     

Thermodynamic,kinetic and structural studies on the mixed ligand complexes of palladium(II) with tridentate and monodentate ligands

Stability constants of the complexes formed in the reaction of [Pd(bpma)](2+) [bpma=bis(pyridin-2-ylmethyl)amine] with monodentate nitrogen and thioether ligands including uridine, MeUH, cytidine, MeC, EtGH, AcHis, AcHm, AcLys and AcMet were determined by potentiometric method. The coordination chemistry of [Pd(bpma)](2+) shows a significant similarity to that of [Pd(terpy)](2+), but it is different from [Pd(dien)](2+). The formation of hydroxo and dinuclear complexes is especially enhanced in the case of [Pd(bpma)](2+) and [Pd(terpy)](2+), but the affinity of palladium(II) ions for the coordination of thioether residues is reduced in the presence of pyridine nitrogen atoms. Stopped-flow kinetic measurements reveal that the substitution reactions of the thioether ligand AcMet are much faster than those of the N-donor cytidine. The presence of the two pyridyl residues significantly enhances the kinetic reactivity of [Pd(bpma)](2+) as compared to that of [Pd(dien)](2+). The Pd-S(thioether) bonded species can be important intermediates in multicomponent systems, but the equilibrium state is characterised by the formation of Pd-N bonded species. The complex [Pd(bpma)NO(3)]NO(3) has been prepared in solid state and its structure was elucidated by single crystal X-ray diffraction method.     

Neuropharmacological actions of some binuclear lanthanide(III) complexes

Binuclear lanthanide(III) compounds are of great interest because of the potential of their mutual Ln(3+)-Ln(3+) electronic couplings to produce unusually sharp images in magnetic resonance and fluorescence imaging of biological tissue. The toxicity and neuropharmacological properties of the water soluble and stable neutral binuclear complex [La(api)](2) were compared with those of binuclear complexes with lower water stability, and the components used in their syntheses. The order of the 24-h LD(50) (mg/kg body wt.) of the compounds in mice was: salicylaldehyde (2.24)160). These compounds induced convulsions, urination and defecation in mice. Due to the relatively very low toxicity of [La(api)](2), its mode of action was explored. Its proconvulsant action may possibly involve an interaction of undissociated complex with muscarinic receptors, and is reversed by atropine.     

Anti-oxidant activity of spermine and spermidine re-evaluated with oxidizing systems involving iron and copper ions

This study was designed to investigate the direction of redox reactions of spermine and spermidine in the presence of iron and copper. The redox activity of spermine and spermidine was assessed using a variety of methods, including their ability to: (1) reduce Fe(3+) to Fe(2+) ions; (2) protect deoxyribose from oxidation by Fe(2+)-ethylene diaminetetraacetic acid, Fe(3+)-ethylene diaminetetraacetic acid systems with and without H(2)O(2); (3) protect DNA from damage caused by Cu(2+)-H(2)O(2), and Fe(2+)-H(2)O(2) with and without ascorbic acid; (4) inhibit H(2)O(2)-peroxidase-induced luminol dependent chemiluminescence; (5) scavenge diphenyl-picryl-hydrazyl radical. Spermine and spermidine at concentration 1mM reduced 1.8+/-0.3 and 2.5+/-0.1 nmol of Fe(3+) ions during 20 min incubation. Both polyamines enhanced deoxyribose oxidation. The highest enhancement of 7.6-fold in deoxyribose degradation was found for combination of spermine with Fe(3+)-ethylene diaminetetraacetic acid. An 10mM spermine and spermidine decreased CuSO(4)-H(2)O(2)-ascorbic acid- and FeSO(4)-H(2)O(2)-ascorbic-induced DNA damage by 73+/-6, 69+/-4% and 90+/-5, 53+/-4%, respectively. They did not protect DNA from CuSO(4)-H(2)O(2) and FeSO(4)-H(2)O(2). Spermine apparently increased the CuSO(4)-H(2)O(2)-dependent injury to DNA. Polyamines attenuated H(2)O(2)-peroxidase-induced luminol dependent chemiluminescence. Total light emission from specimens containing 10mM spermine or spermidine was attenuated by 85.3+/-1.5 and 87+/-3.6%. During 20 min incubation 1mM spermine or spermidine decomposed 8.1+/-1.4 and 9.2+/-1.8% of diphenyl-picryl-hydrazyl radical. These results demonstrate that polyamines of well known anti-oxidant properties may act as pro-oxidants and enhance oxidative damage to DNA components in the presence of free iron ions and H(2)O(2).     

The arsonomethyl group as an analogue of phosphate. An X-ray investigation.

The X-ray structure analysis of three compounds of interest as enzyme substrates is reported. They are the hydrated forms of (I) DL-2-amino-4-arsonobutanoic acid [HO-AsO2--CH2-CH2-CH(NH3+)-CO2H], (II) DL-2-amino-4-phosphonobutanoic acid [HO-PO2--CH2-CH2-CH(NH3+)-CO2H] and the hydrated barium salt of (III) D-3-phosphoglycerate [HO-PO2--O-CH2-CH(OH)-CO2-]. The structures were fully refined to R factors of 0.033, 0.053 and 0.046. For the compounds (I) and (II) the charge distribution was directly determined by locating all H atoms. The co-ordination around As and P is approximately tetrahedral, with the valency angle between the two charged O atoms enlarged to 112 degrees in compound (I), 166 degrees in compound (II) and 122 degrees in compound (III). The As-X bond distances are increased relative to P-X to accommodate the increased atomic radius. The analysis establishes that the compounds are structural analogues. Tables of co-ordinates for H atoms, anisotropic thermal parameters, bond lengths and bond angles for the three compounds have been deposited as Supplementary Publication SUP 50122 (5 pages) with the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained directly [see Biochem J. (1983) 209, 5].